Immune microenvironment of hepatocellular carcinoma,intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma: Relationship with histopathological and molecular classifications

Tumor tissue is composed of tumor cells and tumor stroma. Tumor stroma contains various immune cells and non-immune stromal cells, forming a complex tumor microenvironment which plays pivotal roles in regulating tumor growth. Recent successes in immunotherapies against tumors, including immune checkpoint inhibitors, have further raised interests in the immune microenvironment of liver carcinoma. The immune microenvironment of tumors is formed because of interactions among tumor cells, immune cells and non-immune stromal cells, including fibroblasts and endothelial cells. Different patterns of immune microenvironment are observed among different tumor subtypes, and their clinicopathological significance and intertumor/intratumor heterogeneity are being intensively studied. Here, we review the immune microenvironment of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma, focusing on its histopathological appearance, clinicopathological significance, and relationship with histological and molecular classifications. Understanding the comprehensive histopathological picture of a tumor immune microenvironment, in addition to molecular and genetic approaches, will further potentiate the effort for precision medicine in the era of tumor-targeting immunotherapy.     

复发性肝癌再次手术方式的选择:一项基于倾向评分匹配的研究

目的本研究基于倾向评分匹配(PSM)比较挽救性肝移植(sLT)及再次肝切除(RR)的疗效,同时探讨影响复发性肝癌患者预后的危险因素。方法回顾分析2012年1月至2018年8月宁波大学附属李惠利医院124例肝癌切除术后肝内复发再手术的患者,按照再次所行手术方式的不同,分成sLT组(46例)和RR组(78例),通过1∶1倾向评分匹配(PSM),筛选出34例患者用于数据分析,比较匹配前后两组的临床基本资料、总生存期(OS)及无瘤生存期(DFS)来探讨两种手术方式的优劣以及影响患者预后的因素。结果匹配前sLT组的术前血清总胆红素、多发肿瘤的比例、术前行经导管动脉化疗栓塞术(TACE)的比例及符合米兰标准的比例均要高于RR组(P<0.05),最大肿瘤直径sLT组要小于RR组(P<0.05);手术时间、术中出血量、微血管侵犯(MVI)阳性率及术后ClavienⅢ级以上的并发症的比例均要高于RR组(P<0.05)。匹配后sLT组的手术时间、术中出血量、术后并发症ClavienⅢ以上的比例均高于RR组(P<0.05);sLT组的1、3、5年OS与RR组相比差异无统计学意义(P>0.05),sLT组的1、3、5年DFS与RR组相比较优(P<0.05);甲胎蛋白(AFP)≥100μg/L是OS的独立危险因素,手术方式、AFP≥100μg/L是DFS的独立危险因素。结论sLT组术前病情更重,手术时间、术中出血量及术后严重并发症率高于RR组;sLT组较RR组可取得更长的DFS,但对OS来说,两组之间差异无统计学意义。     

左卡尼汀联合重组人促红素注射液治疗规律透析慢性肾功能衰竭合并贫血患者的临床效果

目的探究左卡尼汀联合重组人促红素注射液治疗规律透析慢性肾功能衰竭合并贫血患者的临床效果。方法选择2017年1月至2020年1月收治的100例规律透析慢性肾功能衰竭合并贫血患者,以计算机随机化法将其分为对照组和试验组,每组50例。对照组给予重组人促红素注射液治疗,试验组给予左卡尼汀与重组人促红素注射液联合治疗。比较两组患者的治疗效果。结果试验组的治疗总有效率为96.00%,高于对照组的80.00%(P<0.05);治疗后,两组患者的MCHC、MCH、MCV、SF、Hb、RBC水平均高于治疗前,且试验组高于对照组(P<0.05);两组患者的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论规律透析慢性肾功能衰竭合并贫血患者接受左卡尼汀与重组人促红素注射液联合治疗,可获得较好的效果,改善贫血相关生化指标水平,且不良反应发生率低,安全有效。     

A Phase I Dose Escalation Study of the Safety,Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors

Lessons Learned

• The overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified.
• The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.

BackgroundThis phase I, open‐label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).MethodsOf 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as “other.” During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3‐week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12‐week cycle, to a maximum of 3 years or PD. Considering the co‐primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose‐limiting toxicities during the 42‐day observation period to proceed with a new cohort of nine patients at 10 mg/kg.ResultsIpilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1–2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti‐ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).ConclusionIpilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.     

Advancement of chimeric antigen receptor-natural killer cells targeting hepatocellular carcinoma

With the advance of genome engineering technology, chimeric antigen receptors (CARs)-based immunotherapy has become an emerging therapeutic strategy for tumors. Although initially designed for T cells in tumor immunotherapy, CARs have been exploited to modify the function of natural killer (NK) cells against a variety of tumors, including hepatocellular carcinoma (HCC). CAR-NK cells have the potential to sufficiently kill tumor antigen-expressing HCC cells, independent of major histocompatibility complex matching or prior priming. In this review, we summarize the recent advances in genetic engineering of CAR-NK cells against HCC and discuss the current challenges and prospects of CAR-NK cells as a revolutionary cellular immunotherapy against HCC.     

Thymic epithelial tumor with superior vena cava syndrome diagnosed by percutaneous endovascular tumor biopsy: A report of two cases

Thymic epithelial tumor is a rare, potentially progressive disease that commonly infiltrates mediastinal structures. In rare cases, it may cause superior vena cava syndrome. Pretreatment histopathological diagnosis is essential to determine the most effective treatment strategy. Percutaneous endovascular biopsy is a rarely reported non-surgical diagnostic option for large vessel tumoral involvement. We report two cases of thymic epithelial tumor with superior vena cava syndrome diagnosed by percutaneous endovascular biopsy. No procedural complications occurred, and subsequent systemic treatment was promptly administered. This procedure may have potential as a useful diagnostic method for patients with mediastinal tumors involving large vessels.     

Using arterial spin labeling blood flow and its histogram analysis to distinguish early-stage nasopharyngeal carcinoma from lymphoid hyperplasia

To investigate the feasibility of arterial spin labeling (ASL) blood flow (BF) and its histogram analysis to distinguish early-stage nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoid hyperplasia (NPLH).Sixty-three stage T1 NPC patients and benign NPLH patients underwent ASL on a 3.0-T magnetic resonance imaging system. BF histogram parameters were derived automatically, including the mean, median, maximum, minimum, kurtosis, skewness, and variance. Absolute values were obtained for skewness and kurtosis (absolute value of skewness [AVS] and absolute value of kurtosis [AVK], respectively). The Mann–Whitney U test, receiver operating characteristic curve, and multiple logistic regression models were used for statistical analysis.The mean, maximum, and variance of ASL BF values were significantly higher in early-stage NPC than in NPLH (all P < 0.0001), while the median and AVK values of early-stage NPC were also significantly higher than those of NPLH (all P < 0.001). No significant difference was found between the minimum and AVS values in early-stage NPC compared with NPLH (P = 0.125 and P = 0.084, respectively). The area under the curve (AUC) of the maximum was significantly higher than those of the mean and median (P < 0.05). The AUC of variance was significantly higher than those of the other parameters (all P < 0.05). Multivariate analysis showed that variance was the only independent predictor of outcome (P < 0.05).ASL BF and its histogram analysis could distinguish early-stage NPC from NPLH, and the variance value was a unique independent predictor.     

Clinical practice guidelines for the interventional treatment of advanced pancreatic cancer (5th edition)

Pancreatic cancer has become a major disease affecting people's health because of its insidiousness, rapid progression and poor prognosis. Based on the practical needs of clinical work, combined with domestic multi-center research and experience, this guideline provides constructive suggestions for the interventional treatment of pancreatic cancer.